Modulation of synaptic plasticity by brain estrogen in the hippocampus
Modulation of synaptic plasticity by brain estrogen in the hippocampus
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DOI：
10.1016/j.bbagen.2009.11.002
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发表时间：
2010-10-01
影响因子：
3
通讯作者：
Ogiue-Ikeda, Mari
中科院分区：
文献类型：
--
作者：
Mukai, Hideo;Kimoto, Tetsuya;Ogiue-Ikeda, Mari
海马体是学习和记忆的中心，也是老年人阿尔茨海默病的目标。雌激素对突触的调节对于了解雌激素替代疗法的分子机制是至关重要的。由于雌激素的局部合成发生在两性的海马中，除了来自性腺的雌激素供应外，其功能也备受关注，海马雌激素对记忆相关突触可塑性的调节不仅缓慢，而且迅速。17 β-雌二醇（17 β-E2）的缓慢作用通过经典的核受体（ER α或ER β）发生，而快速E2作用通过突触定位的ER α或ER β发生。E2浓度的升高或降低迅速改变CA 1-CA 3神经元棘的密度和形态。ER α，而不是ER β，驱动这种棘发生的增强/抑制。激酶网络参与ER α的下游。E2水平的变化可迅速调节长时程抑制而非长时程增强。海马体中的E2水平高达约。男性为8 nM，女性为0.5-2 nM，远高于循环中的水平。许多海马脑片实验通过向E2耗竭的脑片补充E2来测量E2的恢复作用。因此，离体切片实验可用作体内雌激素替代疗法的体外模型，用于循环雌激素耗尽的卵巢切除雌性动物。(C)2009 Elsevier By. All rights reserved.
The hippocampus is a center for learning and memory as well as a target of Alzheimer's disease in aged humans. Synaptic modulation by estrogen is essential to understand the molecular mechanisms of estrogen replacement therapy. Because the local synthesis of estrogen occurs in the hippocampus of both sexes, in addition to the estrogen supply from the gonads, its functions are attracting much attention.Hippocampal estrogen modulates memory-related synaptic plasticity not only slowly but also rapidly. Slow actions of 17 beta-estradiol (17 beta-E2) occur via classical nuclear receptors (ER alpha or ER beta), while rapid E2 actions occur via synapse-localized ER alpha or ER beta. Elevation or decrease of the E2 concentration changes rapidly the density and morphology of spines in CA1-CA3 neurons. ER alpha, but not ER beta, drives this enhancement/suppression of spinogenesis. Kinase networks are involved downstream of ER alpha. The long-term depression but not the long-term potentiation is modulated rapidly by changes of E2 level.Determination of the E2 concentration in the hippocampus is enabled by mass-spectrometry in combination with derivatization methods. The E2 level in the hippocampus is as high as approx. 8 nM for the male and 0.5-2 nM for the female, which is much higher than that in circulation. Therefore, hippocampus-derived E2 plays a major role in modulation of synaptic plasticity.Many hippocampal slice experiments measure the restorative effects of E2 by supplementation of E2 to E2-depleted slices. Accordingly, isolated slice experiments can be used as in vitro models of in vivo estrogen replacement therapy for ovariectomized female animals with depleted circulating estrogen. (C) 2009 Elsevier By. All rights reserved.